Suppository



Fel 5.,-1952 w. G. s'rEvENsoN ETAL 2,584,166

SUPPOSITORY Filed May 25, 1948 atenteci Feb. 5, 1,9512

NITED vSTA'IES lPA'l'rllN'i'lf '2,584,166

v sUPPosI'roRY William of.v stevenspn, Lakeside, Quebec, and

William E. MacKinnon, Montreal, Quebec,l

Canada, assignors 'to Ayerst, McKenna & Harrison Limited', St. Laurent, Quebec,j0anada, a

corporation of Canada Application May 25, 1948,'Se'raFNo. '293058 1o ei'afms. (o1. .16v- 164) f1' INTRODUCTION This invention relates toa medicated bougie.

`These articles are slender elongated rod-like Asuppositories adapted ltofbe :inserted :into .-.restricted ori'ees of the. human .or :animal tbody. For example, .bougies are lused for insertion into 4`the.'urethra of human beings for the treatment Lof `genito urinary infections. ,They are also used rior insertion .into the teat canal of domestic animals, for' example cows, .for the treatment of mastitis.

The articles lhave been Amade from different substances designed either to melt at body temperature or else to dissolve in the secretions. The present. invention deals with the soluble type. These have generally been ymade from mouldable substances .like waxes or from compressible .water-soluble substances, for example carbohydrates like lactose, starch and acacia.

There vare `certain requirements for a bougie, particularly when used in the preferred appli'- cation of the present invention, i. e. for treating .mastitis vin cows. It must ube' suilici'ently slender for insertion into the teat canal vpast the sphincter muscles. `It must, at the same time, beof sulcent volume to contain enough of the medicament to act effectively against the' vinfecting organisms. rThis means that there va .minimum effective length because o'f the small cross-sectional. area'. And, the article must have a breaking strength suciently 'high 'to enable satisfactory insertion under practical conditions. The .material from which the vehicle material or carrier for the medicament is' made must be soluble in the secretions and at the Sametime must .be non-reactive with the medicament which is to carry. In the case of certain medicaments, the moisture content of the vehicle material must be low to avoid deterioration of va medicament, for example in the case ofv penicillin, which is moisture labile. The vehicle material must also be non-toxic and non-irritating to the delicate 'tissues in contact with which it is to come. Finally, the bougie must be so constructedv suitably for 'mass production economically and asepti'cally in'large quantities.

Most prior art devices have one or' another disadvantage which prevents `them' from meeting the requirements just outlined.

THE. APPLICANTS DEVELOPMENT The applicants have now discovered that la bougiemeeting all the aboverequirementscan be .made by dry pressure moulding from 'a vehicle essentially of dry fine-particled material which VYcondition is-f-substan'tially free-flowing, andzwithin which the medicament is dispersed. "llieiap- 'plicants have found that sorbitol has unique and unexpc-:fcted characteristics when used as as a vehicle material in making bougies as described.

Preferably, the' YbodyI of the bougie is made -up of sorbito'l, a mould lubricant, and thelmedicament It 'may 'be desirabletov `substi-,i'nite for part of the' sorbitol an' excipi'ent, iter example 'starch ora sugar, 'forinstanca lactose. P-referred mould lubricants are 'calcium stearato, magnesium "sterate or Jalumirl-um stearato. In preparing the bougie, lthe -sorbitol 'and the 'medic'- a'ment are vcompoinrded together ito-form' a tabletting mix and the bougies are punchedfout Avon Aa -tabletting press-equipped with speciallyvshaped punches. K V

The applicantsalso Jprefer 'to lproviderthe bougies with a thin'coating fof lflm -f'of a material `soluble in -thelbody secretions which Iserves vas a `lubricant and also asa protective-coating. ft'o the sugar vehicle. Preferred materials .tor this purpose `are vthe "polyethylene glycols sold `:under the trade-mark Carbo-waa. particularly those having a high `viscosity such' fas the y1500 to .the 6000. The application -of these lubricating substances can lbe conveniently `etected by' dip- 13mg.

Various medicaments` :may be employed'. VThe applicants l'prefer to use vpenicillin isalts, particular-ly the calci-um 'orv potassium.. Crystalline and amorphousvtypes 1may be fused with crystalline preferred. Other antibioticsfwhich 'are-.non- `irritating tov the mucous. membrane `and nontoxic can be employed', `for example, Astreptomycine. Among other possible `med-icaments.,are "tyrothrycin, the sulfa drugs such- :as -`sulfapyrirl-ine, l`sulfadiazinef and sulfanilanfii'de.;v iacrid'ine dyes 'suchr as acroflavin; Quaternary :ammonium compounds, mercurials, organic :silver preparations such as argyroL-organicfsilver preparations,

.the band at the other side.

60,000 units are effective in suppositories of the dimensions described herein.

The preferred dimensions of the bougie are as follows:

The finishedv bougies are preferably packed in a water and moisture impermeable tube, e. g. glass tube containing several bougies. Desirably, the tube also contains a desiccant to absorb any moisture and lessen the possibility of vdeteriorating the medicament.

The application of the bougie in clinical or veterinary use will be well understood by those skilled in the art.

DETAILED DESCRIPTION p In order to illustrate the invention more fully, reference will now be made to the accompanying drawings in which there is illustrated a preferred embodiment of a bougie according to the invention and a preferred apparatus for making this bougie, and in which:

Figure 1 is an enlarged side elevation of a bougie in accordance with the invention.

Figure 2 is a top plan view of the bougie shown.

in Figurel 1.

Figure 3 is an end elevation of the bougie shown in Figures 1 and 2.

Figure 4 is an exaggerated cross-section along the line 4 4 of Figure l.

Figure 5 is an elevation partly in section of ar glass container enclosing several bougies in accordance with the invention.

Figure 6 is a vertical cross-section through a tabletting press constructed in accordance with the present invention and capable of pressing out bougies such as those shown in Figures l to 4.

Figure 7 is a perspective view of one of the punches of the tablet press of Figure 6.

Referring more particularly to the drawings, the bougie is essentially an elongated slender rod ll which in cross-sectional area is made up vof a pair of spaced apart segmentsintervened by a rectangle and has somewhat the over-all -appearance of a sarcophagus or elongated tablet. vThus, the rod is provided with the arcuate top and bottom faces I5 and I6 rounded as at Il -and I8 preferably at each end. Intervening the arcuate faces is a substantially flat face or band 20 which extends lengthwise along each side of the rod and continues around the end to meet The body of the rod is made up essentially of a normally free-flowing (or precompressed to render free-flowing) fine particled sorbitol, a

medicament and a mould lubricant, and if desired, an excipient material, the body having been compressed under relatively high pressure into a solid self-sustaining mass 22. The body in the preferred form is coated with a thin film 25 of a milk soluble lubricating material, preferably a wax, for example polyethylene glycol.

The strength of the bougie is conveniently measured by a test in which it is retained'in a vise and a weight is suspended from it, usually one inch from the point of retention. This gives a breaking strength figure which is an approximation of the breaking strength required in practice. The applicants prefer a bougie having a breaking strength such that it will support at least 60 grams when the rod is retained in a vise in a horizontal "position and fth'e weight is suspended at one inch from the point of retention. It will be recognized, of course, that the length of the bougie is tied up to some extent with the amount of medicament. It is necessary for high potency bougies to be longer so as to contain -moremedicament. The applicants prefer for high potency `bougies a length of around 43 mm.

i APPARATUS cross-section the die and punch combination of a conventional pharmaceutical tabletting machine modified in accordance with the invention. Within a die 30 having a suitable elongated aperture 32, there operates a lower punch and ejector member 35 and an upper punch 31. The lower punch 35 is adapted te be set at the desired position within the die (depending on the amount of material to be compressed into each article) and also acts 'to eject the compressed bougie from the die. The upper and lower punches 35 and 3l are, in accordance with the present invention, elongated in a lateral direction and substantially of the conformation shown in the drawings, particularly Figures 6 and 7, having indentations 35a and 31a of a special shape to give the curved outer faces of the bougie as illustrated in Figures 1 to 4.

The feeding of the moulding material is adjusted in the well-known manner to provide the y desired content for each bougie and the movement of the punches adjusted as described above to give the desired pressure.

The press is operated in the well-known manner to make a bougie at each stroke of the press. The bougie is automatically ejected by the foot 35 and a fresh batch of powder fed for each stroke of the press. With multiple presses employing this principle, a large number of bougies can be made at one stroke of a punchmounting member carrying a number of punches or in a similar apparatus in which a number of punches work at the same time or in rapid sequence.

The nished article has all the characteristics described above as being desirable in a bougie. It is unusual in the sense that it is made from a normally dry free-flowing material. Usually one would not expect to be able to press-mould an elongated article of this nature having sufcient length and at the same time sufficient strength for use as a bougie. Sorbitol has the unlque characteristic that it is capable of cohesion when subjected to pressure in the manner described.

Figure 5 illustrates a convenient form in which the bougies may be packaged for sale. This container is made up of a bottle 40 having a cork or other suitable closure 4l and sealed by wax or other suitable agentI 42. Inside the container is a desiccant material M adapted to absorb any moisture which may be entrained in the atmosphere in the container. Pads 62 and 43 for example of absorbent cotton intervene the bougies I I which are included to the capacity of the container. A paper envelope 36 is provided for the bottle.

Example Inorder that the invention may be carried out and understood in more detail, a specific example will now be given in which a preferred bougie and its method of manufacture is described in detail.

The analysis of the bougie was substantially as follows:

Dimensions Length-43 mm. Cross-sectional Widthapproximately 2.5 mm. Thickness of wax coating- 0.05 to 0.0125 mm.

Shape Sarcophagal or elongated tablet-shaped Constituents Sorbitol-390 mg.

Calcium penicillin (crystalline) 25,000 International or Oxford units Calcium stearato-25 mg.

Carbowax 4000-25 mg.

Physical characteristics Breaking strength when measured in accordance with test described herein when bougie is retained in a vise and weight is suspended from bougie one inch from point of retention-90 `grams Moisture content finished bougie-less than 1% MANUFACTURE ADVAN TAGES Bougies made according to the present invention have all the characteristics described in the preamble of the specication as being requisite to a satisfactory article. At the same timeV they possess the unique characteristic of being made of a dry powdered material, dry-pressed to have the necessary strength and other characteristics for the purposes described.

The sub-titles used-throughout the specicationare merely to simplify reference thereto and should otherwise be disregarded.

We claim: A

1. A bougie consisting of dry free-flowing comminuted material compressed into the form of. an elongated rod, comprising a medicament and a major amount of sorbitol.

2. Abougie, according to claim 1, having an exterior thin coating of a high viscosity watersoluble polyethylene glycol.

3. A bougie, according to claim 1, wherein the medicament is a penicillin salt.

4. A bougie, according to claim 1, wherein the sorbitol is present in excess of by weight of the body.

5. A bougie consisting of dry free-flowing comminuted material compressed into the form of an elongated rod, comprising a medicament, a mould lubricant and a major amount of sorbitol.

6. A bougie, according to claim 5, wherein the medicament is a penicillin salt.

'7. A bougie, according to claim 5, having an exterior thin coating of a high viscosity watersoluble polyethylene glycol.

8. A bougie particularly adapted to the treatment of bovine mastitis consisting of a rigid elongated rod weighing at least '75 mg. and having a length at least latimes its diameter and composed of dry, free-flowing, compressed comminuted material soluble in the secretions of the mammary glands, said rod comprising as the eiective binding agent a major amount of sorbitol and distributed therethrough a dosage unit effective to combat mastitis.

9. A bougie as defined in claim 8 in which the dosage unit comprises 25,000 units of penicillin.

l0. A bougie comprising a long slender rod of substantially cylindrical form and having a diameter in the neighbourhood of 2.5 millimeters, said rod having been pressed from a composition made up of dry powdered material containing a medicament and a major amount of sorbitol, said composition in compressed form being soluble in the secretions of the mammary glands, said rod being at least 1 centimeter in length, said rod having a breaking strength equivalent to at least 60 grams when a rod of the same cross-sectional dimension is retained securely in a horizontal position at one point and a weight suspended from it one inch from the point of retention.

W. G. STEVENSON. WILLIAM E. MACKINNON.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 398,085 Schmelz Feb. 19, 1889 2,149,005 Bockmuhl Feb. 28, 1939 2,321,694 Miller June 15, 1943 2,498,374 Martin Feb. 21, 1950 FOREIGN PATENTS Number Country Date 208,252 Switzerland Apr. 1, 1940 OTHER REFERENCES Drug and Cosmetic Industry-Oct. 1945, page 532, Amer. J. Pharmacy- April 1941, pp. 134-138. 

